rs1394016

Positions:

• chr3-114191042-G-A
• chr3-114191042-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001282563.2(DRD3):​c.-156+8231C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 151,994 control chromosomes in the GnomAD database, including 23,809 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.52 (23809 hom., cov: 31)
• Consequence: DRD3 NM_001282563.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.50

Genes affected

DRD3 (HGNC:3024): (dopamine receptor D3) This gene encodes the D3 subtype of the five (D1-D5) dopamine receptors. The activity of the D3 subtype receptor is mediated by G proteins which inhibit adenylyl cyclase. This receptor is localized to the limbic areas of the brain, which are associated with cognitive, emotional, and endocrine functions. Genetic variation in this gene may be associated with susceptibility to hereditary essential tremor 1. Alternative splicing of this gene results in transcript variants encoding different isoforms, although some variants may be subject to nonsense-mediated decay (NMD). [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DRD3	NM_001282563.2	c.-156+8231C>T		intron_variant			NP_001269492.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DRD3	ENST00000460779.5	c.-156+8231C>T		intron_variant		2		ENSP00000419402	P1

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79158 AN: 151874 Hom.: 23755 Cov.: 31

Gnomad AFR AF: 0.835

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.495

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.522 AC: 79281 AN: 151994 Hom.: 23809 Cov.: 31 AF XY: 0.520 AC XY: 38637 AN XY: 74296

Gnomad4 AFR AF: 0.835

Gnomad4 AMR AF: 0.510

Gnomad4 ASJ AF: 0.351

Gnomad4 EAS AF: 0.346

Gnomad4 SAS AF: 0.479

Gnomad4 FIN AF: 0.368

Gnomad4 NFE AF: 0.384

Gnomad4 OTH AF: 0.497

Alfa AF: 0.406 Hom.: 15356

Bravo AF: 0.545

Asia WGS AF: 0.452 AC: 1573 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.066
DANN	Benign	0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1394016; hg19: chr3-113909889;